The prognostic impacts of TEA domain (TEAD) transcription factor polymorphisms in Chinese hepatocellular carcinoma patients

TEA domain (TEAD) transcription factors play an important role in hepatocellular carcinoma (HCC) development and progression by regulating the expression of a number of genes. However, the association of their genetic variations with HCC prognosis remains elusive. Seven potentially functional single nucleotide polymorphisms in TEAD1-4 (rs2304733, rs10831923, rs12104362, rs3745305, rs11756089, rs2076173, rs7135838) were genotyped from 331 hepatitis B virus positive HCC patients using the Sequenom MassARRAY iPLEX platform. The TEAD3 rs2076173 C allele and rs11756089 T allele were identified as protective alleles as they were significantly associated with longer median overall survival time (MST). The T allele of rs2076173 was significantly associated with HCC survival independent of age, gender, smoking and drinking status, BCLC stage, and chemotherapy or TACE status (HR = 0.73, 95% CI = 0.56-0.93, P = 0.012). This protective effect was more prominent for patients who were non-drinkers (P for multiplicative interaction = 0.002). Patients had more than one of these protective alleles had significant longer MST of 19.25 months than those had none (MST=12.85 months, adjusted HR = 0.56, 95% CI = 0.33-0.95, P=0.030), especially for those non-drinkers (adjusted HR = 0.48, 95% CI = 0.32-0.74, P = 0.001). These findings suggested that rs2076173 and rs11756089 in TEAD3 gene could serve as genetic markers for favorable survival in the Chinese HCC patients.